Speakers
Brendan Byrne
Peadar McGing
M J Duffy
Republic of Ireland
Session Chair: Brendan Byrne
9.00am Peadar McGing, Biochemical testing of atypical fluids – a personal perspective
9.30am M J Duffy, Circulating tumor DNA (ctDNA): The next major blood-based cancer biomarker?
10.00am Graham Lee, It's a big big problem... happening again and again
The Association of Clinical Biochemists in Ireland has previously published two sets of guidelines, The Biochemistry of Biological Fluids and Guidelines for the Use of Tumour Markers. This session will provide an update on how atypical fluids can be utilised in diagnosis and patient management. It will also provide an insight in to the potential for circulating tumour DNA to be added to the existing panel of tumour markers. Finally, we will focus on Prolactin and whether it’s always necessary to screen for Macroprolactin.
Biochemical testing of atypical fluids – a personal perspective - Peadar McGing
First there was urine, for a few thousand years. Then blood testing was added to the repertoire. For Pathology labs today these body fluids are what are tested for the vast majority of patients. But, as in life, there are always exceptions. Along the way laboratory scientists and clinicians have learned that occasionally testing of other body fluids may be of benefit. In Ireland we have an old saying ‘An rud is annamh is iontach’ which translates as ‘the thing that is rare is wonderful’. This lecture will endeavour to show how atypical fluid clinical biochemistry may be wonderful, but it needs more careful review and oversight than it got throughout the 20th century.
For laboratory purposes ‘atypical fluids’ are any body fluids we test other than blood/plasma or urine. In practice these are almost all transcellular fluids and are of particular interest where disease causes an increase in volume (e.g. pleural effusion or ascites). In such cases removal of fluid is therapeutic and analysis is aimed at helping or confirming diagnosis. Unlike blood, where usually a repeat test is still valid if there is a problem with the initial sample, there is often only one shot at diagnostic testing of an atypical fluid. For CSF the body will still contain sufficient fluid but the lumbar puncture procedure is itself very invasive. Therefore there is an onus on pre-analytical aspects of sampling and all tests that the clinician should require are ordered and analysed. Typical problem areas are when both blood and fluid are required simultaneously, and also when special preservatives are required for some of the tests, e.g. you cannot add in pH testing some hours later.
Test procedures such as Light’s Criteria for distinguishing between exudate and transudate origin of pleural fluids has long been accepted as of clinical value. However it is only recently that we in labs have begun to address the issue of such testing being off-label. Testing of atypical fluids needs at least some in-house verification. EQA of these fluids was non-existent until recently but is now being addressed, at least in part.
This presentation will give a brief overview of atypical fluid biochemistry and how it fits into clinical diagnosis. Some examples will be given of both common and more unusual testing of fluids. The presentation will also give a personal view of how to simply address verification and some warnings on avoiding assumptions regarding our assays.
Circulating tumor DNA (ctDNA): The next major blood-based cancer biomarker? - M J Duffy
Protein-based biomarkers are widely used in monitoring patients with diagnosed cancer. These biomarkers however, lack specificity for cancer and have poor sensitivity in detecting new cancers, early recurrences and monitoring therapy effectiveness. Emerging data suggests that the use of circulating tumor DNA (ctDNA) has several advantages over standard biomarkers including greater specificity, higher sensitivity, a broader range of applications and a shorter half-life.
One of the most exciting possibilities with ctDNA is as a screening test for multiple types of cancer using a single sample of blood. Currently, this possibility is being evaluated in a large randomized prospective trial in the UK using the Galleri test. For patients with an established diagnosis of cancer, ctDNA appears to be superior to radiology and standard biomarkers in detecting early recurrent/metastatic disease. Thus, in patients with surgically resected colorectal cancer, ctDNA was shown to be more sensitive than CEA in detecting residual disease and early recurrence. Similarly, in breast cancer, ctDNA was shown to be more sensitive than CA 15-3 in detecting early recurrences. One of the first established clinical uses of ctDNA is in selecting the most appropriate therapy for patients with specific types of cancer, (e.g., mutation testing of EGFR for predicting response to EGFR inhibitors in patients with non-small cell lung cancer). Compared to the traditional tissue analysis approach for the measurement of therapy predictive biomarkers, use of ctDNA is relatively non-invasive, faster, cheaper and importantly provides a more comprehensive overview of mutations present in a tunor than a single biopsy of tissue.
In contrast to proteins however, ctDNA biomarkers are more expensive to measure, less widely available and have longer turn-around times for reporting. Furthermore, ctDNA assays are less well standardized. Despite these limitations, it is likely that ctDNA measurements, will become more widely available where they will complement existing biomarkers and imaging in detecting and managing patients with cancer. Hopefully, these combined approaches will lead to a better outcome.
It's a big big problem... happening again and again
Hyperprolactinaemia has a broad differential ranging from physiological, pharmacological and pathological causes, which may contribute in isolation or in combination to the biochemical and clinical picture. Patients may present with classical symptoms including galactorrhoea, amenorrhea, infertility and vision disturbances or may be asymptomatic. Treatment for hyperprolactinaemia consequently varies from no treatment to pharmacological and surgical intervention. Obtaining the correct differential diagnosis and management is therefore key. Prolactin is not a tumour specific marker nor does its level consistently correlate with tumour size however its role in helping to identify patients with prolactinoma has been long standing and beneficial. Unfortunately, the ability to specifically measure prolactin (bioactive/monomeric) is affected by cross-reactivity with macroprolactin for which treatment is not recommended. This “big big” issue remains to the present day and is one which faces laboratories time and time again. In the immediate sense, we advocate a need for change to current protocols involving macroprolactin testing!
On completion of his PhD, Brendan went to Beaumont Hospital in Dublin to work as a Clinical Biochemist. He remained there for 20 years, specialising in laboratory aspects of the Neuroendocrine service for both adults and paediatrics. In 2019, he moved to the nearby Mater Misericordiae University Hospital to take up a Principal Clinical Biochemist position. There he continues his interests in Neuroendocrine tumours, plays a major role in departmental quality control and is involved in the provision of an Irish EQA scheme for Clinical Chemistry.
Dr. Peadar McGing is a recently retired Principal Clinical Biochemist, having worked in the Mater Misericordiae University Hospital in Dublin for almost four decades. He graduated from University College Cork with a BSc, adding a PhD and an MSc (Clinical Biochemistry) from Trinity College Dublin, and finally FRCPath. He is also on the European register for Specialists in Laboratory Medicine (EuSpLM). He is the outgoing Secretary of ACBI and co-editor of the ACBI/ACB RoI newsletter Clinical Biochemistry News, as well as being Chair of the Irish External Quality Assessment Scheme (IEQAS).
Peadar’s special interests are in education, fluid biochemistry, tumour markers, EQA, and history of laboratory medicine. He served as Regional Tutor for the Republic of Ireland Region for 13 years and currently lectures to the MSc in Clinical Biochemistry in University College, Dublin as well as contributing to the ACBI FRCPath tutorial group. He is an editor and co-author of the well-known ACBI guidelines on tumour markers and on biochemistry of atypical fluids. His current projects include updating the guideline booklets and writing a biography of Prof. Edmond McWeeney, who in 1891 was the first whole-time Professor of Pathology appointed in Ireland.
Away from Clinical Biochemistry Peadar is an enthusiastic participant in athletics and competes in a wide variety of track and field events.
Professor Duffy who is based at St Vincent’s University Hospital, Dublin and University College, Dublin has an international reputation for his research in cancer biomarkers, having published in excess of 250 papers on the topic. In addition to his research and clinical work, Professor Duffy served as a member of 2 International Expert Panels for establishing guidelines on the clinical use of tumor markers, i.e., the National Academy of Clinical Biochemistry (NACB) (USA) and the European Group on Tumor Markers (EGTM).
Professor Duffy received his BSc (Hons) from the University of Galway and his PhD from the University of Manchester. Over the years, Professor Duffy has received multiple awards for his work on cancer including the Abbott Award of the International Society of Oncology and BioMarkers (ISOBM), the St Luke’s Medal Lecture, the Conway Review Medal Lecture and the Lifetime Achievement Award of the Royal Academy of Medicine in Ireland and the National Committee for Biochemistry Award Medal Lecture of the Royal Irish Academy.
Dr Graham Lee is Consultant Clinical Biochemist at the Mater Misericordiae University Hospital (MMUH) Dublin, Midlands Hospital Mullingar and National Orthopaedic Hospital Cappagh. He trained in the UK where he attained Fellowship of the Royal College of Pathologists. He has experience working in many clinical biochemistry laboratories and healthcare settings in Northern Ireland, East Midlands, London and the Republic of Ireland. He is Associate Professor at UCD where he is course director of the MSc in Clinical and Diagnostic Biochemistry and coordinator of several course modules. He is Past-President of the Association of Clinical Biochemists in Ireland and previous Chair of the ACB’s Republic of Ireland (ROI) region as well as ACB ROI regional tutor. He is a European Specialist in Laboratory Medicine (EuSpLM) and his contributions to the European Federation of Laboratory Medicine include corresponding member of the Task Group for the EFLM’s Post-graduate Syllabus Course and coordinator of the course’s Liver module. He has worked on several Irish national programmes including the National Clinical Programme for Cancer and the National Clinical Programme for Pathology.